Ixabepilone and Carboplatin +/- Bevacizumab in Advanced Non-Small-Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Genentech
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00741988
First received: August 25, 2008
Last updated: March 29, 2013
Last verified: March 2013
  Purpose

This is a multicenter, non-randomized, Phase II study of patients with previously untreated NSCLC not amenable to radiotherapy or surgical treatment. The planned enrollment for this trial is 78 patients (including a 10% rate for inevaluable patients). There will be a total of 39 patients in each cohort (Cohorts A and B).


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Ixabepilone
Drug: Carboplatin
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Ixabepilone and Carboplatin With or Without Bevacizumab in Patients With Previously Untreated Advanced Non-Small-Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The Percentage of Patients Who Experience an Objective Benefit From Treatment


Secondary Outcome Measures:
  • Progression Free Survival, the Length of Time, That Patients Were Alive From Their First Date of Treatment Until Worsening of Their Disease [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Characterization of the Toxicity in Patients With Previously Untreated Advanced NSCLC Treated With Ixabepilone and Carboplatin With and Without Bevacizumab. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 82
Study Start Date: September 2008
Study Completion Date: September 2012
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle.
Drug: Ixabepilone
ixabepilone 30 mg/m2
Other Name: Ixempra
Drug: Carboplatin
carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle.
Other Names:
  • Paraplatin
  • Paraplatin-AQ
Experimental: Cohort B
ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of one 21-day treatment cycle.
Drug: Ixabepilone
ixabepilone 30 mg/m2
Other Name: Ixempra
Drug: Carboplatin
carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle.
Other Names:
  • Paraplatin
  • Paraplatin-AQ
Drug: Bevacizumab
bevacizumab 15 mg/kg on Day 1 of one 21-day treatment cycle.
Other Name: Avastin

Detailed Description:

The trial will include a lead-in phase for each cohort to assess safety. In Cohort A, 10 patients will receive ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle. If no unexpected toxicities occur, Cohort A will open to enrollment. Enrollment for Cohort A will be done in two stages (after the lead-in portion is completed). The first stage for Cohort A will enroll a total of 22 patients (this will include the 10 patients from the lead-in phase). If there are at least 3 responses during stage 1, enrollment for stage 2 will proceed. For stage 2 of the study, 17 additional patients will be enrolled (for a total of 39 patients in Cohort A). During stage 1 and stage 2, patients in Cohort A will receive treatment with ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day 1 of each 21-day treatment cycle. Treatment will continue until disease progression or unacceptable toxicity occurs.

After the lead-in phase for Cohort A is completed, a similar lead-in portion, also consisting of 10 patients, will be done for Cohort B. Patients in Cohort B will receive ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of one 21-day treatment cycle. If no unexpected toxicities occur in this group, Cohort B will open to enrollment. Enrollment for Cohort B will also be done in two stages (after the lead-in portion is completed). The first stage for Cohort B will enroll a total of 22 patients (this will include the 10 patients from the lead-in phase). If there are at least 3 responses during stage 1, enrollment for stage 2 will proceed. For stage 2 of the study, 17 additional patients will be enrolled (for a total of 39 patients in Cohort B). During stage 1 and stage 2, patients in Cohort B will receive treatment with ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of each 21-day treatment cycle. Treatment will continue until disease progression or unacceptable toxicity occurs.

Unexpected toxicities include any grade 4 hematologic toxicity or grade 3/4 non hematologic toxicity that does not reverse within 7 days in more than 2 patients.

Eligible patients will receive ixabepilone, carboplatin, and bevacizumab (bevacizumab will be administered to patients in Cohort B only) at 21-day intervals. Patients will be re evaluated every 6 weeks using computerized tomography (CT) scans. Response to therapy will be assigned using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse et al. 2000) (see Section 7). Patients who have objective response or stable disease will continue treatment for 6 cycles, until the time of tumor progression or intolerable treatment-related side effects. Patients in Cohort B without progressive disease will be eligible to receive bevacizumab monotherapy for 6 additional cycles, or until undue toxicity or tumor progression occurs.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed non-small-cell bronchogenic carcinoma (squamous carcinoma, adenocarcinoma, or large cell carcinoma). Cytologic specimens obtained by brushings, washings, or needle aspiration of the defined lesion are acceptable. Mixed tumors with small-cell anaplastic elements are not eligible.
  2. Patients who have newly diagnosed unresectable stage III or IV disease are eligible. Patients with stage III disease should be ineligible for combined modality therapy
  3. Patients must not have received any prior antineoplastic chemotherapy for metastatic lung cancer prior to study entry.
  4. Patients who have had previous radiotherapy as definitive therapy for locally advanced non-small-cell are eligible as long as the recurrence is outside the original radiation port. Radiation therapy must have been completed greater than 4 weeks prior to registration.
  5. Male or female patients >=18 years of age.
  6. Life expectancy of at least 3 months.
  7. ECOG performance status of <=1.
  8. Measurable disease by RECIST criteria (see Section 7).
  9. Laboratory values as follows:

    • ANC >=1500/mm3 (7 days prior to treatment);
    • Hemoglobin >=8 g/dL;
    • Platelets >=100,000 mm3 (7 days prior to treatment)
    • Bilirubin <=1 x ULN for institution
    • AST/SGOT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases and
    • ALT/SGPT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases
    • Creatinine <=2.0 mg/dL or
    • Calculated (measured) GFR >=40 mL/min
    • PT/INR and PTT <=1.5 x ULN
  10. Peripheral neuropathy <= grade 1.

Exclusion Criteria:

  1. A history of cardiac disease as defined by malignant hypertension, unstable angina, congestive heart failure of > grade 2 per New York Heart Association (NYHA) criteria (see Appendix B), myocardial infarction within the previous 6 months, or symptomatic cardiac arrhythmias.
  2. Metastatic brain or meningeal tumors.
  3. Uncontrolled intercurrent illness.
  4. Chemotherapy, investigational drug therapy, or major surgery ≤ 4 weeks prior to starting study drug, or patients who have not recovered from side effects of previous therapy.
  5. Patient is <=5 years free of another primary malignancy, except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if the other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ.

Exclusion Criteria for Enrollment on Bevacizumab (Cohort B):

  1. Patients with squamous cell histology NSCLC.
  2. Patients who have had a major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury within 1 month of beginning bevacizumab.
  3. Patients who have had primary thoracic radiation within 3 months of beginning bevacizumab.
  4. Fine needle aspiration, core biopsy, mediastinoscopy or other minor surgical procedure within 7 days of beginning bevacizumab.
  5. Patients receiving thrombolytic therapy within 10 days of starting bevacizumab.
  6. Patients with serious non-healing wound, ulcer, or bone fracture.
  7. Patients with evidence of bleeding diathesis or coagulopathy.
  8. Patients with history of hemoptysis (defined as bright red blood of ½ teaspoon or more per episode) within 3 months prior to study enrollment.
  9. Patients with proteinuria at screening, as demonstrated by either:

    • Urine protein : creatinine (UPC) ratio >=1.0 or
    • Urine dipstick for protein >=2+ (patients discovered to have >=2+ proteinuria on dipstick at baseline should undergo a 24-hour urine collection, and must demonstrate <1 g of protein in 24 hours to be eligible).
  10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning bevacizumab.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741988

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Gainsville Hematology Oncology Associates
Gainesville, Florida, United States, 32605
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Montana
Dr. Donald Berdeaux
Great Falls, Montana, United States, 59405
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Genentech
Investigators
Study Chair: David R Spigel, MD Sarah Cannon Research Insititute
  More Information

Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00741988     History of Changes
Other Study ID Numbers: SCRI LUN 179
Study First Received: August 25, 2008
Results First Received: January 23, 2013
Last Updated: March 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Non-Small Cell Lung Cancer
Advanced Disease
Untreated
Ixabepilone
Carboplatin
Bevacizumab

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Bevacizumab
Carboplatin
Epothilones
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014